Exosomes secreted by urine-derived stem cells improve stress urinary incontinence by promoting repair of pubococcygeus muscle injury in rats

Wu, Ruoyu, Chengsheng Huang, Qingkai Wu, Xiang Jia, Mengyu Liu, Zhuowei Xue, Yu Qiu, Xin Niu, and Yang Wang. "Exosomes secreted by urine-derived stem cells improve stress urinary incontinence by promoting repair of pubococcygeus muscle injury in rats." Stem cell research & therapy 10, no. 1 (2019): 80.

Abstract
Background
Previous studies revealed that urine-derived stem cells (USCs) could promote myogenesis after the impairment of the sphincter muscles. However, the effects of exosomes secreted by USCs (USCs-Exo) were not elucidated. Exosomes are nanosized membrane vesicles secreted by the cells. They have been proved to be effective in protecting against tissue injury and therapeutic in tissue repair. USCs are ideal sources of exosomes because of the noninvasive obtaining method and self-renewal abilitiy. This study aimed to show the therapeutic effects of USCs-Exo on improving stress urinary incontinence (SUI).

Methods
Rat SUI models were established in this study using vaginal balloon inflation, and urodynamic and histological examination were carried out after exosome application. The proliferation and differentiation of muscle satellite cells (SCs) were evaluated using EdU, Cell Counting Kit 8, immunofluorescence staining, and Western blot analysis. mRNAs and proteins related to the activation of SCs were detected by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.

Results
After exosome injection, the urodynamic parameters significantly improved and the injured muscle tissue recovered well. The activation, proliferation, and differentiation of SCs were promoted. The phosphorylation of extracellular-regulated protein kinases (ERK) was enhanced. When ERK was inhibited, the promoting effect of USCs-Exo treatment disappeared.

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